Increased lung microvascular permeability has been implicated as a primary cause of noncardiogenic pulmonary edema (permeability edema). Clinical examples of this type of edema include neurogenic pulmonary edema, high altitude pulmonary edema, shock lung, and edema produced by various drugs. We have found that aqueous extracts of lung contain factors which are capable of increasing the permeability of the microcirculation of rat skin and may be permeability mediators in the lung as well. From these extracts we have separated a large molecular weight factor (82,000 MW) with an isoelectric point of 4.2 and a small molecular weight fraction approximately 1,400 MW) which is in the process of being purified. These active components produce immediate-transient type of vascular leakage and appear to be inhibited by antihistamines. During the coming year the goals of this project are: (1) to purify the small molecular weight factor and to prepare a sufficient amount of the large molecular weight factor for in vitro and in vivo testing, and (2) to test the ability of these agents to release histamine from isolated mast cells, and (3) develop an in vivo model which will demonstrate whether or not these factors can alter the vascular permeability of the lung. The finding that the lung contains factors which release endogenous histamine would appear to be potentially quite important to our understanding of the pathophysiology of pulmonary edema and may be of therapeutic importance.